Project Summary/Abstract Deficits in attention predict a diminished quality of life and are common in many neuropsychiatric conditions, including schizophrenia, depression, and addiction. The development of improved treatments for attentional dysfunction requires a better understanding of the neural circuitry underlying this fundamental cognitive process. Top-down or goal-directed attention involves the direction of cognitive resources to salient stimuli in accordance with an organism?s goals and expectations; this process is distinct from involuntary attention. Top-down attention deficits are notably characteristic of neuropsychiatric disorders. In top-down attention states, frontal cortices, such as the anterior cingulate cortex (ACC) in mice, exhibit activity before the onset of visual cues. This anticipatory activity modulates sensory and association cortices, such as visual (V1/V2) and parietal association (PtA) cortices in mice. However, the neural circuits mediating this intercortical communication are poorly understood. Preliminary data in mice suggests 1) that the claustrum provides a functional link between ACC and PtA; and 2) that inactivating ACC ? claustrum afferent activity before the onset of a visual cue disrupts performance on a goal-directed attention task. Thus, we hypothesize that the ACC transmits top-down attention signals to the claustrum and that the claustrum propagates ACC input to distal cortical areas necessary for visual attention. To test this novel hypothesis in Aim 1, we use time correlated single photon counting-based in vivo fiber photometry in freely behaving mice to determine if ACC afferents to the claustrum are active during goal-directed attention. In Aim 2, we test if claustrum projection neurons to V1/V2 and PtA are faithfully driven by optogenetic ACC afferent stimulation to determine if the claustrum propagates incoming ACC signals to visual-processing cortical areas. Thus, this proposal utilizes state-of-the-art techniques for an unprecedented look at the circuits, physiology, and behaviors underlying the attention construct as defined by the National Institute of Mental Health Research Domain Criteria framework. Finally, this proposal outlines a rigorous training regimen for the development of an independent researcher, which includes the submission of multiple peer-reviewed publications, the frequent presentation of results at local, national, and international venues, and training in innovative techniques.